Prasad Padala, M.D., an associate director for clinical programs at the Geriatric Research Education and Clinical Center at the Central Arkansas Veterans Healthcare System, and colleagues also found that methylphenidate improved cognition, functional status, caregiver burden, Clinical Global Impression (CGI) scores, and depression.
Padala and colleagues randomized 60 community-dwelling male veterans with mild Alzheimer’s disease to methylphenidate or placebo. All participants were started on 5 mg of methylphenidate or a look-alike placebo twice daily and titrated to 10 mg twice daily at two weeks. The protocol allowed the study physician to decrease the dose if adverse events were reported. Otherwise, participants continued to take 10 mg twice daily until 12 weeks, at which time the dose was tapered to 5 mg twice daily for three days and stopped.
The primary outcome measure was the score on the clinician-reported Apathy Evaluation Scale (AES-C). The secondary outcome measures were scores on the Modified Mini-Mental State Examination and instruments evaluating cognition and function, including ability to carry out daily activities, and depression.
Padala and colleagues found significant differences over time for apathy in the methylphenidate group but not in the placebo group. After adjusting for baseline scores on the AES-C, they found that the methylphenidate group had significantly greater improvement than the placebo group at four weeks, and apathy continued to improve at eight weeks and 12 weeks. The behavioral and cognitive domains improved by eight weeks, and the emotional domain finally improved at 12 weeks.
“These results suggest that improvement in the emotional domain may be mediated by improvements in the cognitive and behavioral domains,” Padala and colleagues wrote.
They added, “Although the ideal duration of treatment with methylphenidate is unknown, a case for longer duration can be made because the results of these studies were proportional to the duration of treatment, with the highest improvement in apathy and cognition noted with 12-week treatment. Longer duration studies need to be conducted to investigate if the improvement in apathy continues with the duration of treatment or if it plateaus at a certain point.”
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